Unit on Neuroscience and Novel Therapeutics

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

First, in 2023, our program submitted a manuscript based on our completed the first multiple baseline novel frustration-exposure intervention for youth with severe irritability based on extinction principles. The results of the study are under review; N=41 youth were randomized; preliminary analyses demonstrated that irritability scores decreased significantly from the start of therapy to end of therapy. We acquired pre-treatment behavioral and task-based fMRI data to test the hypothesis that pre-treatment behavioral deficits in inhibition predict poorer treatment response. Second, in 2023, we had a paper accepted for publication examining the brain changes associated with cognitive behavioral therapy in youth with anxiety. Across two randomized controlled trials, unmedicated children with an anxiety disorder diagnosis completed task-based functional magnetic resonance imaging pre- and post-treatment. For benchmarking purposes, age-matched healthy comparison youth completed two scans over the same time span. Pretreatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy control children. Hyperactivation in fronto-parietal networks normalized over treatment, whereas limbic response remained elevated post-treatment. Findings inform future treatment studies and suggest the potential value of adjunct treatments that more directly target limbic change to enhance cognitive behavioral therapy (CBT) efficacy. Third, we leveraged technology to assess symptoms by utilizing digitally based event sampling (ecological momentary assessment). Last year we validated our metric. This year, we published two additional papers. We identified the central symptoms associated with irritability and demonstrated differences in fluctuations in positive and negative affect in youth with different psychiatric disorders. In addition, we developed a cognitive inhibition mobile application to probe children's inhibitory control. Over 200 youth have completed the task remotely. Data demonstrate the validity, and reliability of the mobile app relative to in clinic standardized behavioral tasks. Results are being written up for publication. Together, these mobile assessments provide the foundation for scalable, target-based interventions which are more easily disseminated, facilitating public health impact. Fourth, as threats engage evolutionarily conserved processes, our translational perspective has been supported by two Bench-to-Bedside Awards. Specifically, we reverse translated the Human Intruder Paradigm into two clinical paradigms. Our fMRI (N=130) and eye-tracking (N=60) tasks parallel work in non-human primates. Data analyses are ongoing. Ultimately, these mechanistic studies will allow for more targeted interventions for pathological irritability.